We have identified activated transforming genes from more than 20 mouse and human T- and B-lymphocyte neoplasms by transfection of NIH 3T3 cells. By restriction enzyme analysis we have identified common genes activated within neoplasms of a particular differentiated phenotype. We have thus far identified 5 different genes activated in these T and B-lymphocyte neoplasms. The first gene is common to four human pre-B tumors; the second is common to three mouse B-lymphomas; the third is common to two human myelomas and two mouse plasmacytomas; the fourth is common to 6 mouse T-lymphomas and 1 human T-lymphoma; and the fifth is common to a human sezary syndrome neoplasm and a mouse Lyl+ helper phenotype tumor. In these studies, we will use monoclonal antibodies generated by other investigators to these neoplasms to identify cell surface proteins induced or coded for by the transforming genes. We will clone a representative transforming gene from each of the 5 categories identified. These genes will be analyzed to define the alterations in the DNA which lead to their activation, and will be used as probes to study their activation in response to the appropriate signals during normal cell proliferation.